Document Detail


Germ-free C57BL/6J mice are resistant to high-fat-diet-induced insulin resistance and have altered cholesterol metabolism.
MedLine Citation:
PMID:  20724524     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Recent studies showed that germ-free (GF) mice are resistant to obesity when consuming a high-fat, high-carbohydrate Western diet. However, it remains unclear what mechanisms are involved in the antiobesity phenotype and whether GF mice develop insulin resistance and dyslipidemia with high-fat (HF) feeding. In the present study, we compared the metabolic consequences of HF feeding on GF and conventional (conv) C57BL/6J mice. GF mice consumed fewer calories, excreted more fecal lipids, and weighed significantly less than conv mice. GF/HF animals also showed enhanced insulin sensitivity with improved glucose tolerance, reduced fasting and nonfasting insulinemia, and increased phospho-Akt((Ser-473)) in adipose tissue. In association with enhanced insulin sensitivity, GF/HF mice had reduced plasma TNF-α and total serum amyloid A concentrations. Reduced hypercholesterolemia, a moderate accretion of hepatic cholesterol, and an increase in fecal cholesterol excretion suggest an altered cholesterol metabolism in GF/HF mice. Pronounced nucleus SREBP2 proteins and up-regulation of cholesterol biosynthesis genes indicate that enhanced cholesterol biosynthesis contributed to the cholesterol homeostasis in GF/HF mice. Our results demonstrate that fewer calorie consumption and increased lipid excretion contributed to the obesity-resistant phenotype of GF/HF mice and reveal that insulin sensitivity and cholesterol metabolism are metabolic targets influenced by the gut microbiota.
Authors:
Sylvie Rabot; Mathieu Membrez; Aurélia Bruneau; Philippe Gérard; Taoufiq Harach; Mireille Moser; Frederic Raymond; Robert Mansourian; Chieh J Chou
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-08-19
Journal Detail:
Title:  FASEB journal : official publication of the Federation of American Societies for Experimental Biology     Volume:  24     ISSN:  1530-6860     ISO Abbreviation:  FASEB J.     Publication Date:  2010 Dec 
Date Detail:
Created Date:  2010-12-02     Completed Date:  2011-01-04     Revised Date:  2012-02-15    
Medline Journal Info:
Nlm Unique ID:  8804484     Medline TA:  FASEB J     Country:  United States    
Other Details:
Languages:  eng     Pagination:  4948-59     Citation Subset:  IM    
Affiliation:
Institut National de Recherche Agronomique, UMR1319 Micalis, Jouy-en-Josas, France.
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MeSH Terms
Descriptor/Qualifier:
Animals
Blotting, Western
Body Weight / physiology
Cholesterol / metabolism*
Dietary Fats / adverse effects*
Germ-Free Life
Glucose Tolerance Test
Glycogen / metabolism
Insulin Resistance / physiology*
Lipids / blood
Liver / metabolism
Male
Mice
Mice, Inbred C57BL
Obesity / blood,  metabolism
Oligonucleotide Array Sequence Analysis
Polymerase Chain Reaction
Chemical
Reg. No./Substance:
0/Dietary Fats; 0/Lipids; 57-88-5/Cholesterol; 9005-79-2/Glycogen

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